This ongoing study is split into parts. Part 1 included patients with high-intermediate or high-risk DLBCL who were administered 1.2 or 1.8mg/kg brentuximab vedotin plus RCHOP. However, 3 of the initial 10 patients treated at the 1.8mg/kg dose level developed grade 3 peripheral neuropathy and so all further patients enrolled received treatment at the lower dose of 1.2mg/kg brentuximab vedotin plus RCHOP. After enrollment was completed for Part 1, a protocol amendment took place for a non-randomized portion of the study (Part 2; NCT01925612) aimed at determining the efficacy and safety of 6 cycles 1.8mg/kg brentuximab vedotin plus RCHP. Part 3 is an open-labelled, randomized study comparing brentuximab vedotin + RCHP to RCHOP. This presentation included initial results from Part 2 and updated results from Part 1.

Part 2

At time of analysis, 11 patients were treated (7 males, 4 female, 22–78 years of age)

Resolution of all or some of the peripheral neuropathy occurred in 21/38 patients (55%)

It was concluded that 1.8mg/kg brentuximab vedotin plus RCHP is an effective frontline therapy in high-intermediate/high-risk DLBCL expressing CD30 and appears well tolerated.

Abstract

Introduction: DLBCL is the most common lymphoid neoplasm in adults (Swerdlow 2016). While durable CRs are achieved in approximately 70% of patients (pts) with frontline RCHOP therapy (Pfreundschuh 2008), pts with high-risk features often experience disease resistance or relapse. In Part 1 of an ongoing study, pts with high-intermediate or high risk DLBCL by international prognostic index (IPI) scores, regardless of CD30 expression by IHC, were treated with 1.2 or 1.8 mg/kg brentuximab vedotin (BV) combined with RCHOP. After 3 of the first 10 pts treated at 1.8 mg/kg BV+RCHOP developed Grade 3 peripheral neuropathy (per Standardized MedDRA Query [SMQ]), all pts enrolled subsequently received treatment with 1.2 mg/kg BV+RCHOP. Following completion of enrollment in Part 1, the protocol was amended to enroll a non-randomized portion of the study (Part 2) evaluating the safety and efficacy of 1.8 mg/kg BV+RCHP (Yasenchak 2015), followed by an open-label, randomized portion comparing BV+RCHP to RCHOP (Part 3). Initial results from Part 2 and updated results from Part 1 are reported here.

Methods: For Part 2 of the study, pts with CD30-expressing high-intermediate and high-risk DLBCL were treated with up to 6 cycles of 1.8 mg/kg BV+RCHP (NCT01925612). Key inclusion criteria were CD30 expression by IHC performed by a local pathology lab and standard IPI scores of 3–5 or age-adjusted IPI (aaIPI) scores of 2–3 (high-intermediate/high risk). CD30 expression was confirmed by a central pathology lab, although CD30 expression by local pathology lab was required for eligibility. Disease response was evaluated with PET/CT per Cheson 2007.

Results: At the time of analysis for this ongoing study, 11 pts in Part 2 were treated with BV+RCHP (7 male, 4 female; 22‑78 yrs). Of these pts, 9 had high-intermediate risk (IPI 3, aaIPI 2) and 2 had high risk disease (IPI 4-5, aaIPI 3), 6 had Stage IV disease, and 6 had an ECOG score of 2. At the end of treatment, the overall response rate was 91% (9 CR, 1 PR); 1 pt had PD after Cycle 4. The most frequent (>20%) treatment-emergent adverse events (AEs) were alopecia and nausea (73% each); fatigue (64%); constipation and peripheral sensory neuropathy (55% each); neutropenia and throat irritation (36% each); and chills, diarrhea, headache, and stomatitis (27% each). Grade 3 or 4 AEs occurred in 8 pts and 5 pts had serious AEs, which included febrile neutropenia, bacteremia, nausea, pneumocystis jiroveci pneumonia, pulmonary embolism, and vomiting. Peripheral sensory neuropathy occurred in 6 pts and all were Grade 1 or 2 events; no peripheral motor neuropathy AEs were reported. No AEs were fatal or led to discontinuation. One pt discontinued treatment after Cycle 4 due to disease progression.

Conclusions: 1.8 mg/kg BV+RCHP is active as frontline treatment in CD30-expressing, high-intermediate/high risk DLBCL. When combined with RCHP, 1.8 mg/kg BV appears to be well-tolerated. The PFS and OS for pts with CD30-expression who received BV+RCHOP appear promising. The study is currently ongoing in pts with CD30-expressing high-intermediate/high risk DLBCL to assess the safety and activity of 1.8 mg/kg BV+RCHP versus standard RCHOP.

Mar 21, 2018

Jan 31, 2018

Nov 14, 2016

Professional society

The European Lymphoma Institute is comprised of a network of top European specialists in the field of lymphoma who are dedicated to research, training and education. Together they look to define strategies to analyse and characterize lymphoma and its common diagnostic procedures and therapeutic standards, as well as to facilitate clinical and fundamental research. This all results in the advancement of lymphoma research and it guarantees equal access for all patients to the best possible care.